A meta-analysis of the impact of IVF and ICSI on major malformations after adjusting for the effect of subfertility.

OBJECTIVE: To estimate the effect of assisted reproductive technology (ART) on major malformation (MM) rate in ART offspring independent of the effect of subfertility on MM. DESIGN: Meta-analysis. METHODS: This meta-analysis is based on our previously published meta-analysis of observational studies evaluating the relationship between ART treatment and MM rates, as well as recent research by Zhu et al. to estimate the impact of subfertility alone on MM in subfertile couples conceiving spontaneously. RESULTS: The overall odds ratio for MM in our original meta-analysis, in which all studies used apparently inappropriate control groups of "normal" populations, was 1.29 (95% CI 1.01-1.67). Here we attempted to estimate the risk of subfertility and used this estimate to perform an adjusted meta-analysis. Zhu et al. found that about 40% of the odds of MM was due to subfertility. When we took Zhu's finding into account, the adjusted odds ratio in the meta-analysis was 1.01 (95% CI 0.82-1.23). CONCLUSIONS: Our study suggests ART does not increase the risk of MM as much as previously reported. More research is needed to quantify the underlying risk of subfertility and separate it from the risk associated with ART. Physicians who counsel subfertile couples should recognize that previous studies of MM rates in ART patients probably overestimated the risk.

Post-acute care services received by older adults following a cardiac event: a population-based analysis.

BACKGROUND: Post-acute care (PAC) is available for older adults who need additional services after hospitalization for acute cardiac events. With the aging population and an increase in the prevalence of cardiac disease, it is important to determine current PAC use for cardiac patients to assist health care workers to meet the needs of older cardiac patients. The purpose of this study was to determine the current PAC use and factors associated with PAC use for older adults following hospitalization for a cardiac event that includes coronary artery bypass graft and valve surgeries, myocardial infarction (MI), percutaneous coronary intervention (PCI), and heart failure (HF). METHODS AND RESULTS: A cross-sectional design and the 2003 Medicare part A database were used for this study. The sample (n = 1493521) consisted of patients 65 years and older discharged after their first cardiac event. Multinomial logistic regression was used to examine factors associated with PAC use. Overall, PAC use was 55% for cardiac valve surgery, 50% for MI, 45% for HF, 44% for coronary artery bypass graft, and 5% for PCI. Medical patients use more skilled nursing facility care, and surgical patients use more home health care. Only 0.1% to 3.4% of the cardiac patients use intermediate rehabilitation facilities. Compared with those who do not use PAC, those who use home health care and skilled nursing facility care are older and female, have a longer hospital length of stay, and have more comorbidity. Asians, Hispanics, and Native Americans were less likely to use PAC after hospitalization for an MI or HF. CONCLUSIONS: The current rate of PAC use indicates that almost half of nondisabled Medicare patients discharged from the hospital following a cardiac event use one of these services. Health care professionals can increase PAC use for Asians, Hispanics, and Native Americans by including culturally targeted communication. Optimizing recovery for cardiac patients who use PAC may require focused cardiac rehabilitation strategies.

Putative Gonadotropin-Releasing Hormone Agonist Therapy and Dementia: An Application of Medicare Hospitalization Claims Data.

BACKGROUND: Estrogen and hormone replacement therapies to reduce Alzheimer's disease (AD) have yielded conflicting results. However, this study proposes that the well-characterized increase in serum gonadotropins following menopause or andropause are accountable for the increased risk of developing AD among the elderly population. OBJECTIVE: To determine the role of gonadotropins in the development of AD and investigate gonadotropin-releasing hormone (GnRH) agonist therapy as a potential preventative and/or disease-modifying approach to AD management. METHODS: Male Medicare beneficiaries aged 67 to 75 and hospitalized with prostate cancer (n = 115,789) were compared to three control groups: men of the same demographics undergoing a cholecystectomy (n = 97,267), herniorrhaphy (n = 68,778), or transurethral prostatectomy (n = 267,691). A proportion of the patients hospitalized with prostate cancer were assumed to have low concentrations of serum gonadotropins and sex steroids as a result of GnRH agonist therapy, while those in the control groups were assumed to have elevated gonadotropin but lowered sex steroid levels that are associated with andropause in this age group. RESULTS: The rates of development of select diagnoses of dementia, including AD, over a twelve-year follow-up period following surgery. When compared to control patients, men hospitalized with prostate cancer have a protection against dementia after twelve years of follow-up, with relative risks ranging from 0.48 to 0.83. CONCLUSION: Patients with prostate cancer are treated with the GnRH analogue leuprolide acetate, our data suggest that leuprolide acetate may be therapeutic for AD via its downregulation of serum gonadotropins.

Geographic and patient variation in receipt of surveillance procedures after local excision of cutaneous melanoma.

Little is known about variation in surveillance practices following the diagnosis of invasive melanoma. The objective of this study was to characterize geographic, patient, and tumor variation in the use of follow-up surveillance testing in patients with local or regional stage melanoma. A cohort of Medicare beneficiaries > or =65 y diagnosed with invasive melanoma during 1992 to 1996 living in a Surveillance, Epidemiology, and End Results registry area was studied. Outpatient and inpatient Medicare claims 3 mo following diagnosis were examined for up to 2 y for surveillance procedures of interest. Use of chest X-ray, chest computed tomography scan, abdominal and/or pelvic computed tomography scan, abdominal ultrasound, head computed tomography scan, head magnetic resonance imaging, laboratory testing, and skin examinations were compared between patient groups and geographic regions. A total of 3389 patients were identified for the analysis. Surveillance testing was relatively common, ranging from 13% for abdominal ultrasound to 80% for laboratory testing. Follow-up skin examinations were performed in 70% to 90% of patients. The use of most surveillance procedures was associated (p<0.01) with younger age, male gender, regional stage tumors, and geographical area, with up to 2-fold differences observed. In contrast, there was much less variability in the receipt of skin examinations. Further studies are needed to determine the etiology and impact of such disparities, and the influence of surveillance procedures on morbidity and mortality.

The "Adequacy of Prenatal Care Utilization" (APNCU) index to study low birth weight: is the index biased?

A recent, nationwide study of 54 million births reported increasing trends toward more prenatal resource utilization from 1981 to 1995, when other indicators have shown worsening trends in birth outcomes. The Adequacy of Prenatal Care Utilization (APNCU) Index was used to measure resource utilization, but the Index appears to be biased because women grouped in the intensive category have the highest rates of low birth weight (LBW). The objective of this paper is to provide a systematic examination of the Index and to uncover biases that may preclude its use in analyzing the association between resource utilization and birth outcomes. This is a cross-sectional study including all singleton live births in 1993 through 1996 (n = 591,403) in Ohio. Birth certificate data are used to derive the Index, which categorizes women as follows: Adequate Plus (A+), Adequate, Intermediate, and Inadequate. The Index is based on the ratio of observed to expected (O/E) number of prenatal visits. The expected number of visits is based on the American College of Obstetricians and Gynecologists (ACOG) recommendations. The Index also considers the month of initiation of prenatal care. The outcome measures are low birth weight (LBW) and small-for-gestational age (SGA). The LBW rate is 11.8% in the (A+) category, compared to 9.4% in the Inadequate category, and 3.3% and 3.5% in each of the Intermediate and Adequate categories, respectively. Preterm births are disproportionately represented in the (A+) category: 61.2% of births prior to 37 weeks are (A+), whereas only 18.9% of term births are (A+). This apparent bias results from the fact that the ACOG schedule of prenatal visits allocates nearly one third of the total visits to the last 4-5 weeks of gestation. A shorter gestational age implies fewer number of expected visits, a smaller denominator in the O/E ratio, and O/E ratios exceeding 100% by large margins. In fact, the observed number of visits exceeds the expected number of visits by only one or two in 40.1% of all births grouped in the (A+) category. Consequently, the Index yields misleading results indicating that women grouped in the (A+) category (or O/E ratios > 110%) are most likely to deliver LBW infants. Contrary to the results obtained through the APNCU Index, our gestational age-specific analysis showed that increasing number of prenatal visits is associated with improved birth outcomes. We recommend that the use of the APNCU Index to study the association between prenatal resource utilization and LBW be discontinued.

Ability of Medicaid claims data to identify incident cases of breast cancer in the Ohio Medicaid population.

BACKGROUND: The use of Medicaid data to study cancer-related outcomes would be highly desirable. However, the accuracy of Medicaid claims data in the identification of incident cases of breast cancer is unknown. OBJECTIVES: (1) To estimate the sensitivity of Medicaid claims data for case ascertainment of breast cancer, and (2) to determine the positive predictive value (PPV) of diagnostic and procedure codes retrieved from Medicaid claims, using the Ohio Cancer Incidence Surveillance System (OCISS) as the gold standard. METHODS: The study used the linked OCISS and Medicaid enrollment files, 1997-1998 (n = 1,648). The claims search yielded 2,635 incident cases, of which 1,132 were also identified through the OCISS-Medicaid files. Sensitivity and PPV of Medicaid data were calculated in subgroups of the population. RESULTS: The overall sensitivity was 68.7 percent, but varied greatly across the subgroups of the population. It was lower among women enrolled in Medicaid only for part of the study year than those enrolled in Medicaid for 12 months of the study year (56.7 percent and 78.0 percent respectively, p < 0.0001), and lower among those who are dual Medicare-Medicaid eligible compared to those not participating in the Medicare program (63.1 percent and 78.6 percent respectively, p < 0.0001). The overall PPV was 43.0 percent, increasing up to 86.6 percent in the presence of procedure codes indicating the presence of mastectomy and lumpectomy, in addition to that of breast cancer diagnosis. CONCLUSIONS: The sensitivity of Medicaid claims for case ascertainment of breast cancer is somewhat low, but improves considerably when accounting for women enrolled in Medicaid for the entire duration of the study year. The PPV is poor due to a high rate of false positives. The higher PPV obtained in the presence of procedure codes, in addition to diagnosis codes, will help researchers to correctly identify incident cases of breast cancer using Medicaid claims data.

The impact of delayed chemotherapy on its completion and survival outcomes in stage II colon cancer patients.

BACKGROUND: Delayed chemotherapy is associated with inferior survival in stage III colon and stage II/III rectal cancer patients, but similar studies have not been performed in stage II colon cancer patients. We investigate the association between delayed and incomplete chemotherapy, and the association of delayed chemotherapy with survival in stage II colon cancer patients. PATIENTS AND METHODS: Patients (age ≥ 66) diagnosed as stage II colon cancer and received chemotherapy from 1992 to 2005 were identified from the linked SEER-Medicare database. The association between delayed and incomplete chemotherapy was assessed using unconditional and conditional logistic regressions. Survival outcomes were assessed using stratified Cox regression based on propensity score matched samples. RESULTS: 4,209 stage II colon cancer patients were included, of whom 73.0% had chemotherapy initiated timely (≤ 2 months after surgery), 14.7% had chemotherapy initiated with moderate delay (2-3 months), and 12.3% had delayed chemotherapy (≥ 3 months). Delayed chemotherapy was associated with not completing chemotherapy (adjusted odds ratio (OR): 1.33 (95% confidence interval: 1.11, 1.59) for moderately delayed group, adjusted OR: 2.60 (2.09, 3.24) for delayed group). Delayed chemotherapy was associated with worse survival outcomes (hazard ratio (HR): 1.75 (1.29, 2.37) for overall survival; HR: 4.23 (2.19, 8.20) for cancer-specific survival). CONCLUSION: Although the benefit of chemotherapy is unclear in stage II colon cancer patients, delay in initiation of chemotherapy is associated with an incomplete chemotherapy course and poorer survival, especially cancer-specific survival. Causal inference in the association between delayed initiation of chemotherapy and inferior survival requires further investigation.

Radiotherapy and survival in prostate cancer patients: a population-based study.

PURPOSE: To investigate the association of overall and disease-specific survival with the five standard treatment modalities for prostate cancer (CaP): radical prostatectomy (RP), brachytherapy (BT), external beam radiotherapy, androgen deprivation therapy, and no treatment (NT) within 6 months after CaP diagnosis. METHODS AND MATERIALS: The study population included 10,179 men aged 65 years and older with incident CaP diagnosed between 1999 and 2001. Using the linked Ohio Cancer Incidence Surveillance System, Medicare, and death certificate files, overall and disease-specific survival through 2005 among the five clinically accepted therapies were analyzed. RESULTS: Disease-specific survival rates were 92.3% and 23.9% for patients with localized vs. distant disease at 7 years, respectively. Controlling for age, race, comorbidities, stage, and Gleason score, results from the Cox multiple regression models indicated that the risk of CaP-specific death was significantly reduced in patients receiving RP or BT, compared with NT. For localized disease, compared with NT, in the monotherapy cohort, RP and BT were associated with reduced hazard ratios (HR) of 0.25 and 0.45 (95% confidence intervals 0.13-0.48 and 0.23-0.87, respectively), whereas in the combination therapy cohort, HR were 0.40 (0.17-0.94) and 0.46 (0.27-0.80), respectively. CONCLUSIONS: The present population-based study indicates that RP and BT are associated with improved survival outcomes. Further studies are warranted to improve clinical determinates in the selection of appropriate management of CaP and to improve predictive modeling for which patient subsets may benefit most from definitive therapy vs. conservative management and/or observation.

Mammography utilization rates among young white and black women in the USA.

OBJECTIVE: To determine mammography utilization rates for randomly selected white and black women in the USA. STUDY DESIGN: This was an observational study using data from 1988 to 2000. Data were extracted from the Behavioral Risk Factor Surveillance System, an annual self-report telephone survey conducted nationally by the Centers for Disease Control and Prevention. METHODS: The main outcome measure was the mammography utilization rates of women ages 18-40 years responding to 'Have you ever had a mammogram?'. In total, 354097 women were included in this study [310336 (87.6%) white women and 43761 (12.4%) black women]. RESULTS: In women ages 18-33, black women showed consistently higher mammography utilization rates than white women. Utilization rates among women ages 18-23 years were 20.0% and 11.0% for black and white women, respectively. Among women ages 24-29 years, rates were 22.2% and 11.5% for black and white women, respectively. For women ages 30-33 years, rates were 25.7% and 18.1% for black and white women, respectively. Utilization rates were similar in black and white women over 33 years of age. CONCLUSIONS: This study found that young black women were receiving more mammography screening than young white women between 1988-2000. This may be due to the increased risk of fibroid masses in young black women.

Air pollution and emergency department visits for asthma among Ohio Medicaid recipients, 1991-1996.

We examined the effects of nitrogen dioxide (NO(2)), ozone (O(3)), particulate matter of <10 microm aerodynamic diameter (PM(10)), and sulfur dioxide (SO(2)) on asthmatics ages 5-34 years enrolled in Medicaid in Cincinnati, Cleveland, and Columbus, OH (N=5416). Our study period was for the summer months, June-August, from July 1, 1991 to June 30, 1996. We preformed Poisson regression analyses for the number of daily emergency department (ED) visits for asthma in each city and on the aggregate data controlling for time trends and minimum temperature. We found a 12% increased likelihood of an asthma ED visit per 50 microg/m(3) increase in PM(10) in Cleveland [95% confidence interval (CI)=0-27%] and a 35% increase per 50 microg/m(3) increase in SO(2) in Cincinnati (95% CI=9-21%). When data were analyzed for all three cities combined, the risk of an ED visit increased for all pollutant increases and specifically by 12% (95% CI=1-23%) per 50 microg/m(3) increase in SO(2). Attributable risk estimates show a five times greater impact on Cleveland over Cincinnati or Columbus. Between 1991 and 1996, air pollutants in Cincinnati, Cleveland, and Columbus increased ED visits for asthmatics enrolled in Medicaid.

Association of prediagnosis endoscopy with stage and survival in adenocarcinoma of the esophagus and gastric cardia.

BACKGROUND: Barrett esophagus, a consequence of chronic gastroesophageal reflux disease, is a premalignant condition for adenocarcinoma of the esophagus and, possibly, the gastric cardia. However, the actual use and clinical impact of upper gastrointestinal endoscopy in screening and surveillance for Barrett esophagus are unknown. METHODS: A cohort included 1633 patients with adenocarcinoma (777 esophagus, 856 cardia) who were 70 years or older. They were diagnosed between 1993 and 1996 and were identified from the Surveillance, Epidemiology and End Results program registry. All claims for upper endoscopy and a diagnosis of Barrett esophagus from 1991 through 1 year before diagnosis were identified from linked Medicare files. RESULTS: One or more upper endoscopies before diagnosis were performed in 9.7% of patients (13.0% esophagus, 6.8% cardia) and a diagnosis of Barrett esophagus was present in only 3.7% of patients. A shift toward earlier stage at diagnosis was observed in patients with previous endoscopy or Barrett diagnosis. For example, 62% of patients with esophageal and 49% of patients with cardia tumors who underwent previous endoscopy presented with in situ or local stage carcinoma, compared with 35% and 27% of other patients, respectively. Receipt of endoscopy was also associated with a reduced risk of death for esophageal adenocarcinoma (relative hazard 0.73, 95% confidence interval 0.57-0.93; P = 0.01), but not for adenocarcinoma of the cardia. CONCLUSIONS: Receipt of upper endoscopy at least 1 year before diagnosis of adenocarcinoma, which may reflect prediagnosis screening, was associated with an earlier tumor stage and improved survival. These data support the role of endoscopic screening and surveillance for Barrett esophagus and highlight the underdiagnosis of populations at risk.

Use of Medicare claims data to measure county-level variation in breast carcinoma incidence and mammography rates.

BACKGROUND: National-level population-based data about breast carcinoma incidence and its association with screening mammography are currently not available. METHODS: Inpatient, hospital outpatient and physician/supplier Medicare claims were used to identify incident cases of breast carcinoma in women > or = 65 years from 1996 to 1997 and calculate county-level incidence rates. The 1994-1995 claims data were used to determine county-level rates of mammography, and determine the correlation with incidence. RESULTS: The median 2-year incidence rate for women > or = 65 was 979/100,000, and substantial variation in incidence between counties was observed. (i.e. 25th percentile 789/100,000, 75th percentile 1186/100,000). Two-year county-level mammography rates also varied among counties (i.e. 25th percentile 30.5%, 75th percentile 40.9%) and were higher in white women than in black women (median 36.8 and 26.3%, respectively). Counties with higher rates of mammography also had higher age-adjusted incidence rates. CONCLUSIONS: Medicare claims may provide an alternative source of population-based data, particularly for areas in which registry data are not readily available, or are of limited scope. The data highlight the geographic variation in incidence and screening rates that may be useful for targeted interventions, and also suggest that mammography remains in a growth phase.

A meta-analysis of controlled studies comparing major malformation rates in IVF and ICSI infants with naturally conceived children.

PURPOSE: To estimate the risk of major malformations in IVF and ICSI infants. METHODS: Forty-four studies published in English since 1990 where the major malformation rate for IVF or ICSI cases was compared to an appropriate control group were reviewed. Nineteen studies met all selection criteria. In addition, a quality score was developed to assess each study based on sample size, timing of diagnosis, appropriateness of control group and other factors. RESULTS: In 19 studies, the major malformation rates ranged from 0-9.5% for IVF; 1.1-9.7 for ICSI; and 0-6.9% in the control groups. When ICSI was compared to IVF, and multiple births compared to singleton, there were no statistically significant differences. When data from 16 studies involving 28,524 IVF infants and 2,520,988 spontaneously conceived controls and 7 studies involving 7234 ICSI infants and 978,078 controls were pooled, we found an overall odds ratio for the 19 studies of 1.29 (95% CI 1.01-1.67). CONCLUSIONS: The overall odds ratio of 1.29 was statistically significant at the 5% level. These results may be useful for counseling ART patients and properly designing the consent forms used for ART procedures. It is not clear whether this risk is due to the procedures used in ART. We found that some of these studies have design flaws. All of them lacked an appropriate control group, i.e. infertile patients conceiving spontaneously. These flaws may create biases that would in almost all instances increase the risk of major malformations in the study group. Further research with better designed studies will likely result in a better estimate of the risk of major malformations associated with IVF and ICSI.

The sensitivity of Medicare data for identifying incident cases of invasive melanoma (United States).

BACKGROUND: The completeness of Medicare claims for identifying patients with melanoma for purposes of conducting population-based studies of melanoma is unknown. METHODS: Using a linked Surveillance, Epidemiology, and End Result (SEER) tumor registry-Medicare database, the sensitivity of Medicare claims for identifying 5372 patients age > or =65 years diagnosed with invasive melanoma between 1992 and 1996 was determined. Sensitivity was calculated as the proportion of incident cases of melanoma reported by SEER that was also captured by Medicare claim diagnostic codes. RESULTS: The overall sensitivity of combined Part A and Part B Medicare for incident cases of melanoma was 90.1%. Part B Medicare and Part A Medicare alone had 89.5% and 16.5% sensitivity respectively. Sensitivity was lower for patients with unrecorded Breslow depth and for patients with unstaged or distant stage melanoma. CONCLUSIONS: Medicare Part B claims have a high sensitivity for detecting melanoma incidence; Medicare Part A has low sensitivity. This sharply contrasts with published studies of other cancers, for whom Part A rather than Part B Medicare captures the predominant portion of incident cases. Medicare Part B or combined Part A and Part B administrative data is a potentially valuable resource for population-based melanoma research in the elderly. Further research characterizing the specificity and predictive value of Medicare data is needed to assess the potential implications of false positive melanoma diagnostic codes.